Automatic analyzer and operating method for same

ABSTRACT

An automatic analyzer is free from limitations on layout of various mechanisms, and thus causing no bottlenecks, for example, in a space-saving design of the automatic analyzer. This invention includes a coaxial planar duplex arrangement of two dilution disks each with annularly disposed dilution cells, and the dilution disks A and B operate independently of each other. Various mechanisms (parent-sample sampling mechanism, diluent delivery mechanism, diluent/sample mixing mechanism, and diluted-sample sampling mechanism) used in a dilution process can each access the two dilution disks. The dilution process for a parent sample, executed on the dilution disks A and B, can be continuously conducted by providing a fixed delay in operational timing between the two dilution disks.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to automatic analyzers forclinical laboratory tests, and to methods of operating such an automaticanalyzer. More particularly, the invention is directed to diluting aparent sample.

2. Description of the Related Art

In automatic analyzers for clinical laboratory tests, reduction in theamount of reaction liquid to be used for analysis is required forreduction in running costs associated with laboratory tests. The amountof reaction liquid is proportional to the amount of sample to be usedfor the analysis. To reduce the amount of reaction liquid, therefore, itis absolutely necessary that the amount of sample be reduced to a verysmall level. At the current technical level of sampling, however,significant reduction in the amount of reaction liquid is difficultsince quantitative minimization of sampling has its limit.

Accordingly, microsampling generally uses sample dilution.JP-A-08-194004 proposes a method of diluting a sample.

SUMMARY OF THE INVENTION

The dilution of a sample usually uses a dilution disk.

The dilution disk with an annular array of dilution cells rotates insingle-step feed mode, and the distance through which the disk moves inone rotation is equivalent to a number without a common factor withrespect to the total number of dilution cells present on the disk.

When the dilution disk repeating the above rotation is in a stoppedcondition, various mechanisms that access the dilution disk (namely, aparent-sample sampling mechanism, a diluent delivery mechanism, a mixingmechanism, and a diluted-sample sampling mechanism) conduct aparent-sample dilution process (parent-sample sampling, diluentdelivery, diluent/sample mixing, and diluted-sample sampling).

During the sample dilution process based on this scheme, however, thedilution disk rotates with the above-defined number as its single-stepfeed rate. That is to say, the above four mechanisms (the parent-samplepipetting mechanism, the diluent delivery mechanism, the mixingmechanism, and the diluted-sample pipetting mechanism) perform therespective functions during the stopped state of the dilution disk.

This means that the layout of each mechanism which accesses the dilutiondisk is limited, which, in turn, may cause bottlenecks, for example, inthe space-saving design of the analyzer.

With the above problem taken into account, the present invention has anobject to provide an automatic analyzer free from limitations on layoutof various mechanisms, and thus causing no bottlenecks, for example, ina space-saving design of the automatic analyzer.

An aspect of the present invention, an automatic analyzer comprises: asample array storage unit including a sample disk on which parent samplecontainers each for accommodating a parent sample are arrayed; areaction disk with reaction cells arrayed thereon; a dilution disk withdilution cells annularly arrayed thereon; a parent-sample samplingmechanism for pipetting each parent sample from the sample array storageunit into each dilution cell; a diluent delivery mechanism fordelivering a liquid diluent to the dilution cell having the parentsample pipetted thereinto; a mixing mechanism for mixing the pipettedparent sample and the diluent; a diluted-sample sampling mechanism forpipetting into one of the reaction cells a diluted sample created bymixing the parent sample and the diluent in the dilution cell; andcontrol means that conducts operational control of the above-describedtypes of disks and mechanisms; wherein the control means uses a controlfunction to ensure that successive actions in a dilution process for theparent sample, that is, parent-sample sampling, diluent delivery,diluent/sample mixing, and diluted-sample sampling are sequentiallyconducted for one arbitrarily selected dilution cell on the dilutiondisk.

In the dilution process for the parent sample, therefore, each mechanismcan freely determine an access position with respect to the dilutiondisk because of no limitations on the rotation of the disk.

In another aspect of the present invention, two dilution disksconstructed to rotate concentrically about a common axis are arranged intwo rows, one to form an inner peripheral region and the other to forman outer peripheral region, and the two dilution disks operateindependently of each other.

In yet another aspect of the present invention, various mechanisms thatare used in a dilution process for a parent sample (namely, aparent-sample sampling mechanism, a diluent delivery mechanism, a mixingmechanism, and a diluted-sample sampling mechanism) are each disposed tobe able to access two dilution disks, and are each constructed to movedilution cells to accessible positions according to particularrotational movements of the dilution disks and sequentially conduct thedilution process in each dilution cell.

In a further aspect of the present invention, when two dilution disksexist, successive actions in a dilution process for a parent sample,that is, parent-sample sampling, diluent delivery, diluent/samplemixing, and diluted-sample sampling are sequentially conducted using onearbitrarily selected dilution cell on each dilution disk. After thedilution process using the arbitrarily selected dilution cell, theassociated dilution disk rotates and the next dilution process using adilution cell located next to the selected one is started.

The dilution process for the parent sample is executed with a definitedelay in operational timing between the two dilution disks. While thediluted sample is being pipetted using one dilution disk A,parent-sample sampling, diluent delivery, and diluent/sample mixing areexecuted using other dilution disk B. After diluted-sample sampling onthe dilution disk A, the pipetting action immediately changes todiluted-sample sampling on the dilution disk B.

Since the execution timing of the dilution process is delayed betweenthe two dilution disks in this manner, the parent sample can be dilutedefficiently and continuously.

According to the present invention, because of no limitations on therotation of the dilution disk(s), each of the parent-sample samplingmechanism, diluent delivery mechanism, diluent/sample mixing mechanism,and diluted-sample sampling mechanism used in the dilution process forthe parent sample can freely determine an access position with respectto the dilution disk(s) . Flexibility of the layout of each mechanismimproves, which is very beneficial for design purposes such as apparatusspace saving.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram relating to an embodiment of the present invention,illustrating the overall configuration of an automatic analyzer forclinical laboratory tests; and

FIG. 2 is a diagram relating to the embodiment of the present invention,illustrating in detail the configuration concerned with a dilutionprocess for a parent sample.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Embodiments of the present invention will be described in detail,pursuant to FIGS. 1 and 2.

A first embodiment of the present invention is described below.

FIG. 1 is a total apparatus block diagram of a biochemical automaticanalyzer used in the present invention.

The automatic analyzer has a sample disk 2 (sample array storage unit)for accommodating parent samples 1 that were taken into test tubes orthe like, a dilution disk 3 for diluting the parent samples 1, a reagentcoolbox 5 for cold storage of reagent bottles 4, and a reaction disk 6for causing a reaction of a reaction liquid while rotating cyclically atfixed intervals.

Each parent sample 1 is suctioned by a parent-sample sampling mechanism7 and then pipetted into any one of dilution cells 8 arrayed on thedilution disk 3. A liquid diluent is delivered from a diluent deliverymechanism 9 to the dilution cell 8 into which the parent sample 1 hasbeen pipetted, and the parent sample and the diluent are stirred andmixed by a diluent/sample mixing mechanism 10. The sample that has beendiluted on the dilution disk 3 is suctioned by the diluted samplesampling mechanism 11 and then pipetted into any one of reaction cells12 arrayed on the reaction disk 6.

A reagent is added to the diluted sample by a suctioning action of areagent-sampling mechanism 13 from one of the reagent bottles 4, andafter the diluted sample and the reagent have been made to react in thereaction cell 12, absorbance is measured with a spectrophotometer 14.Measured data is collected into a computer 50 (a controller), andanalytical results are output therefrom. The dilution cell 8 is cleanedby a cleaning mechanism 15 and later reused.

The computer 50 (controller) is used to control the operation of theabove-described types of disks and mechanisms. The computer 50 uses acontrol function to ensure that in the dilution process for the parentsample, successive actions of parent-sample sampling, diluent delivery,diluent/sample mixing, and diluted-sample sampling are sequentiallyconducted for one arbitrarily selected dilution cell on the dilutiondisk.

According to the above control function, each of the parent-samplesampling mechanism, diluent delivery mechanism, diluent/sample mixingmechanism, and diluted-sample sampling mechanism used in the dilutionprocess for the parent sample can freely determine an access positionwith respect to the dilution disk because of no limitations on rotationthereof. Each mechanism improves in flexibility of layout, and thisimprovement becomes very beneficial for design purposes such asapparatus space saving.

The controller also has a control function that controls the operationof each type of disk and each kind of mechanism so that after thedilution of the parent sample using one dilution cell, the dilution diskrotates and the next dilution process using a dilution cell located nextto that dilution cell is conducted.

In this way, the dilution process that uses dilution cells is repeatedfor each cell in sequential feed mode, so the rotation of the dilutiondisk through one full turn allows all cells to be used and operation tobe controlled easily.

FIG. 2 is a detailed diagram illustrating the dilution process for theparent sample.

Two dilution disks that rotate concentrically about a common axis arearranged in two rows, one to form an inner peripheral region and theother to form an outer peripheral region, and the two dilution disks canoperate independently of each other. Dilution cells 18 are arrayedannularly on the dilution disk A 16 and the dilution disk B 17.

An example in which a total number of dilution cells present on the twodilution disks is 60 (30 each) is described below.

A parent-sample sampling mechanism 19, a diluent delivery mechanism 20,a diluent/sample mixing mechanism 21, a diluted-sample samplingmechanism 22, and a dilution cell cleaning mechanism A 23 and a dilutioncell cleaning mechanism B 24 access the two dilution disks at aparent-sample pipetting position A 25 and parent-sample pipettingposition B 26, a diluent delivery position A 27 and a diluent deliveryposition B 28, a diluent/sample mixing position A 29 and adiluent/sample mixing position B 30, a diluted-sample suction position A31 and a diluted-sample suction position B 32, and a dilution cellcleaning position A 33 and a dilution cell cleaning position B 34,respectively. These access positions are shown in FIG. 2. The dilutiondisks rotate to move the dilution cells 18 to each position fordilution.

The two dilution disks are arranged within a spatial range over whichsuccessive actions of each mechanism extend. Thus, one particularmechanism can access the two dilution disks. Also, this arrangement ofthe dilution disks makes it unnecessary to provide independentmechanisms for each dilution disk, and hence simplifies theconfiguration of the apparatus.

In addition, since the two dilution disks rotate independently of eachother, operation of each kind of mechanism can be executed for eachdilution disk. Thus, a total processing time can be reduced since, whileone dilution disk is being used for sampling the diluted sample, theother dilution disk can be used to execute parent-sample sampling,diluent delivery, and diluent/sample mixing.

Furthermore, since the two dilution disks are arranged to rotateconcentrically about a common axis are arranged planarly in two rows,one to form an inner peripheral region and the other to form an outerperipheral region, the layout of the dilution disks, compared withseparate layout of each, is compact and convenient for configuring theapparatus such that one mechanism accesses the two dilution disks.

Tables 1 and 2 list actions of each mechanism for the dilution disk A 16and the dilution disk B 17 shown in FIG. 2.

TABLE 1

TABLE 2

Hyphenated numerals in the table (i.e., 1-A to 30-A, 1-B to 30-B) denotedesignation numbers of the dilution cells present on the two dilutiondisks (for convenience' sake, these numbers are simply shown as 1 to 30in FIG. 1). The dilution process is conducted at positions listed in aboldface box in the table. This table assumes one-sample two-itemanalysis, in which analysis the pipetting of one diluted sample into areaction cell 36 is repeated twice.

The dilution process for the parent sample includes four actionscontrolled by a control function of a computer 50 (controller) . Thefour actions are listed below.

(1) Parent-Sample Sampling Action

A parent sample 38 is suctioned from a sample disk 37 by theparent-sample sampling mechanism and then pipetted into a dilution cell18 present on the dilution disk.

(2) Diluent Delivery Action

A liquid diluent is delivered from the diluent delivery mechanism 20 tothe dilution cell 18 into which the parent sample 38 has been pipetted.

(3) Diluent/Sample Mixing Action The parent sample 38 and the diluentare stirred and mixed using the diluent/sample mixing mechanism 21.

(4) Diluted-Sample Sampling Action

The sample that has been diluted by stirring and mixing is suctioned bythe diluted-sample sampling mechanism 22 and then pipetted into areaction cell 36 present on a reaction disk 35.

As listed in Tables 1 and 2, parent-sample sampling action (1) isexecuted in the first cycle using a dilution cell (No. 1-A) of thedilution disk A 16. In the second cycle, the dilution disk A 16 rotatesand diluent delivery action (2) and diluent/sample mixing action (3) areconducted in that order for the dilution cell (No. 1-A).

In the third to fourth cycles, the dilution disk A 16 rotates anddiluted-sample sampling action (4) is conducted for the dilution cell(No. 1-A). In the fifth cycle, after the diluted-sample sampling action,the dilution disk A 16 rotates, and control moves to the next dilutionprocess that uses an immediately next dilution cell (No. 30-A).

While the diluted sample is being pipetted in the third to fourth cyclesusing the dilution disk A 16, dilution process actions (1) to (3) areconducted on the dilution disk B 17 using a dilution cell (No. 1-B).

In the fifth cycle, after diluted-sample sampling on the dilution disk A16, diluted-sample sampling action (4) is conducted for the dilutioncell (No. 1-B). In the seventh cycle, after diluted-sample samplingaction (4) for the dilution cell (No. 1-B), the dilution disk B 17rotates, and control moves to the next dilution process that uses animmediately next dilution cell (No. 30-B).

In the fifth to sixth cycles, dilution process actions (1) to (3) areconducted on the dilution disk A 16 using a dilution cell (No. 30-A). Inthe seventh cycle, after diluted-sample sampling into the dilution cell(No. 1-B), control moves to the pipetting of the diluted sample into adilution cell (No. 30-A).

Continuous dilution can be conducted in this manner by assigning a fixeddelay in the execution timing of the dilution process between the twodilution disks. Since the dilution process is repeated for multipledilution cells in succession, the total processing time can be reduced.

Before being reused, the dilution cell 18 is cleaned by the dilutioncell cleaning mechanism A 23 and the dilution cell cleaning mechanism B24. The dilution cell cleaning mechanism A 23 conducts a dilution cellcleaning action for the dilution disk A 16 while the parent-samplesampling mechanism 19 is accessing the dilution disk A 16. The dilutioncell cleaning mechanism B 24 conducts a dilution cell cleaning actionfor the dilution disk B 17 while the diluted-sample sampling mechanism22 is accessing the dilution disk B 17.

As listed in Tables 1 and 2, the two dilution disks continuously conductthe dilution process while using immediately next dilution cells. Inthis case, if one rotation cycle of the reaction disk 35 is sevenseconds long, it takes 700 seconds (100 cycles) for a specific dilutioncell to arrive at the dilution cell cleaning position after thediluted-sample sampling action.

A time of 600 seconds is usually required from completion of thediluted-sample sampling action to output of analytical results, and thedilution disk can hold the diluted sample for a time required forcompletion of confirming whether re-analysis for reasons such as ananalytical error is necessary. If the re-analysis is necessary, thedilution disk is rotated and after the dilution cell containing thediluted sample has been moved to the diluted-sample suction position,the diluted-sample sampling action is immediately re-executed. There-analysis can thus be conducted rapidly.

For analysis of hemoglobin “Alc”, after the parent sample 38 has beendiluted, there is a need to leave this diluted sample intact in thedilution cell for a fixed time until the diluted sample has beenpipetted into the next dilution cell. For this analytical item, afterdilution process actions (1) to (3) have been executed, diluted-samplesampling action (4) is skipped and the next dilution process ispreferentially conducted. After a lapse of a necessary time, thedilution disk is rotated, then the dilution cell containing the dilutedsample is moved to the diluted-sample suction position, anddiluted-sample sampling action (4) is executed.

In the clinical automatic analyzer of the present invention thatinvolves sample dilution using dilution disks, the layout of theparent-sample sampling mechanism, diluent delivery mechanism,diluent/sample mixing mechanism, and diluted-sample sampling mechanismused in the dilution process can be freely determined, which alleviateslimitations on apparatus design.

1. An automatic analyzer comprising: a sample array storage unit including a sample disk on which parent sample containers each for accommodating a parent sample are arrayed; a reaction disk with reaction cells arrayed thereon; a dilution disk with dilution cells annularly arrayed thereon; a parent-sample sampling mechanism for pipetting each parent sample from the sample array storage unit into each dilution cell; a diluent delivery mechanism for delivering a liquid diluent to the dilution cell having the parent sample pipetted thereinto; a mixing mechanism for mixing the pipetted parent sample and the diluent; a diluted-sample sampling mechanism for pipetting into one of the reaction cells a diluted sample created by mixing the parent sample and the diluent in the dilution cell; and control means that controls operation of each kind of mechanism as well as operation of each kind of disk; wherein the control means has a control function that works such that in a dilution process for the parent sample, successive actions of parent-sample sampling, diluent delivery, diluent/sample mixing, and diluted-sample sampling are sequentially conducted for one arbitrarily selected dilution cell on the dilution disk.
 2. The automatic analyzer according to claim 1, wherein: the control means has a control function that controls the operation of each disk and each mechanism such that after the dilution process using the arbitrarily selected dilution cell, the dilution disk rotates and a next dilution process is conducted using a dilution cell located next to the selected cell.
 3. The automatic analyzer according to claim 1, further comprising: two dilution disks that operate independently of each other; wherein the two dilution disks are arranged within a spatial range over which the successive actions of the mechanisms extend.
 4. The automatic analyzer according to claim 3, wherein: the two dilution disks rotate concentrically about a common axis and are arranged in two rows, one to form an inner peripheral region and the other to form an outer peripheral region.
 5. The automatic analyzer according to claim 3, wherein: the control means has a control function that works such that while one dilution disk is being used for pipetting the diluted sample, the other dilution disk is used to execute parent-sample sampling, diluent delivery, and diluent/sample mixing sequentially, and such that after the pipetting of the diluted sample using the dilution disk, the diluted sample is immediately pipetted from the other dilution disk.
 6. The automatic analyzer according to claim 5, wherein: the control means has a control function that works such that after analysis using the diluted sample, the dilution disk holds the diluted sample for a time it takes for completion of confirming whether re-analysis is necessary, and such that if the re-analysis is necessary, the dilution disk rotates and after the dilution cell containing the diluted sample has been moved to a diluted-sample suction position, the diluted-sample sampling action is repeated once again.
 7. The automatic analyzer according to claim 5, wherein: the control means has a control function that works such that for an analytical item requiring the diluted-sample sampling action, after the diluted sample has been left intact in the dilution cell for a fixed time, the pipetting of the diluted sample is skipped for a fixed time and the next dilution process is preferentially conducted, the control function further working such that after a lapse of a necessary time, the dilution disk rotates, then the dilution cell containing the diluted sample is moved to the diluted-sample suction position, and the diluted-sample sampling action is executed.
 8. A method for operating an automatic analyzer including: a sample array storage unit including a sample disk on which parent sample containers each for accommodating a parent sample are arrayed; a reaction disk with reaction cells arrayed thereon; a dilution disk with dilution cells annularly arrayed thereon; a parent-sample sampling mechanism for pipetting each parent sample from the sample array storage unit into each dilution cell; a diluent delivery mechanism for delivering a liquid diluent to the dilution cell having the parent sample pipetted thereinto; a mixing mechanism for mixing the pipetted parent sample and the diluent; a diluted-sample sampling mechanism for pipetting into one of the reaction cells a diluted sample created by mixing the parent sample and the diluent in the dilution cell; and control means that controls operation of each kind of mechanism as well as operation of each kind of disk; wherein the control means conducts control such that in a dilution process for the parent sample, successive actions of parent-sample sampling, diluent delivery, diluent/sample mixing, and diluted-sample sampling are sequentially conducted for one arbitrarily selected dilution cell on the dilution disk. 